title: Phytohemagglutinin-induced IL2 mRNA in whole blood can predict bortezomib-induced peripheral neuropathy for multiple myeloma patients.
abstract: The proteasome inhibitor bortezomib has revolutionized the treatment of multiple myeloma. However, bortezomib-induced peripheral neuropathy (BiPN) is a serious complication that compromises clinical outcome. If patients with a risk of developing BiPN could be predicted, physicians might prefer weekly, reduced-dose, or subcutaneous approaches. To seek biomarkers for BiPN, we conducted a multicenter prospective study using a simple and unique system. Multiple myeloma patients received twice-weekly or weekly 1.3 mg/m(2) bortezomib intravenously, and a 2-ml sample of whole blood was obtained before treatment and 2-3 days and 1-3 weeks after the first dose. Induction of gene expression was then quantified by real-time PCR. Of a total of 64 enrolled patients, 53 patient samples qualified for mRNA analysis. The BiPN grade was associated with phytohemagglutinin-induced IL2, IFNG and TNFSF2, as well as with lipopolysaccharide-induced IL6 levels. More importantly, of the 19 patients showing a 3-fold increase in phytohemagglutinin-induced IL2, 14 did not suffer from BiPN (73.7% prediction), whereas of the 34 patients with a <3-fold increase, 23 experienced BiPN (67.6% prediction). Therefore, we concluded that pretreatment of phytohemagglutinin-induced IL2 mRNA levels in whole blood serve as a promising biomarker for predicting BiPN, and this finding warrants validation in a larger study.
authors.affiliation: Hematology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Mitsuhashi
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authors.initials: M
authors.lastname: Sagawa
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authors.initials: M
authors.lastname: Ri
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
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authors.initials: M
authors.lastname: Abe
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authors.initials: K
authors.lastname: Ohmachi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Chosa
authors.forename: S
authors.initials: S
authors.lastname: Iida
authors.forename: M
authors.initials: M
authors.lastname: Kizaki